P1176: CLINICAL OUTCOMES OF NOVEL THERAPIES IN RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA
Authors: Jennifer Crombie, Monika Jun, Tongsheng Wang, Alex Mutebi, Anthony Wang, Anindit Chibber, Rajesh Kamalakar, Jon Ukropec, Julie Blaedel, Anupama Kalsekar
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have had historically poor outcomes with evidence of progressively lower response rates as they advance through lines of therapy (LOT). Despite recent treatment approvals by the US Food and Drug Administration and European Medicines Agency in this setting, a need to enhance our understanding of the efficacy of these therapies in clinical practice persists. Novel treatments for patients with R/R DLBCL include chimeric antigen receptor T-cell (CAR T) therapy, polatuzumab vedotin plus bendamustine and rituximab (pola-BR), tafasitamab plus lenalidomide (tafa-len), loncastuximab (lonca), and selinexor. Aims: The objective of this study was to examine real-world outcomes of these novel therapies. Methods: Patient data from the COTA electronic health records database (2010–2021) were used for this retrospective study. The COTA database uses deidentified electronic health record data from various academic or for-profit community sites and hospital systems in the US. To be considered for the analyses, patients had a diagnosis of DLBCL after January 1, 2010, with ≥1 prior line of systemic antineoplastic therapy (including an anti-CD20 antibody), and treatment with any of these novel therapies. Patients receiving variations of pola-BR or tafa-len regimens were included. Outcomes included overall response rate (ORR), complete response (CR) rate, median progression-free survival (mPFS), and median overall survival (mOS). Outcomes were also analyzed for those treated with any novel therapy following prior CAR T exposure. Results: A total of 175 patients with R/R DLBCL (60.6% male, median age 63 y) who had failed ≥1 prior LOT were included in the study. Among these patients, 29.1% had an International Prognostic Index score ≥3, 61.7% had stage III/IV disease, and 65.7% had primary refractory disease. For those treated with CAR T, pola-BR, and tafa-len regimens, a total of 73, 69, and 27 patients were treated, respectively. Only 6 patients were treated with lonca; no patients were treated with selinexor. Among 169 patients treated in the 2L+ setting (CAR T, pola-BR, and tafa-len regimens, respectively), the ORR was 76.7%, 59.4%, and 40.7%, and the CR rate was 52.1%, 18.8%, and 11.1% (Table). A total of 112 patients that failed ≥1 prior LOT also failed ≥2 prior LOT. For this group (CAR T, pola-BR, and tafa-len regimens, respectively), the ORR was 74.6%, 62.2%, and 35.0%, and the CR rate was 41.8%, 13.5%, and 10.0%. Among the 18% of patients treated with a novel agent after CAR T exposure, ORR was 19.1%, CR rate was 4.8%, mPFS was 1.4 mo, and mOS was 2.3 mo. Summary/Conclusion: Outcomes for patients treated with pola-BR and tafa-len–based regimens remain suboptimal. These outcomes appear to worsen as patients advance to subsequent LOT, with particularly worse outcomes when new treatments are used after CAR T therapy.Keywords: Real world data, Non-Hodgkin’s lymphoma, Clinical outcome, Survival